Staphylococcus aureus causes disease chiefly through the production of virulence factors such as hemolysins, enterotoxins and toxic shock syndrome toxin. The synthesis of virulence factors in S. aureus is controlled by a regulatory RNA molecule, RNAHI (Novick, etal., EMBO J. 12, 3967 (1993), Balaban et al., FEMS Microbiol Letts. 133, 155 (1995), Moerfeldt et al., EMBO J. 14, 4569 (1995)), encoded by the agr locus. The rnaiii gene of the agr locus is transcribed in culture only from the midexponential phase of growth, and is autoinduced by the protein RNAIII activating protein (RAP) (Balaban et al., Proc. Natl. Acad. Sci. USA. 92,1619 (1995)). RAP is continuously secreted by the bacteria and only activates RNAIII at a concentration threshold (ibid).
The growth-phase associated regulation of S. aureus virulence factor synthesis is controlled by a quorom sensing mechanism. The control of virulence factor production is a complex process, which apparently involves multiple global regulatory loci. One of these regulatory loci, the agr locus, contains two divergent transcription units, RNAII and RNAIII, both of which are active only from the midexponential phase of growth and are autocatalytic (Novick et al. Mol. Gen. Genet. 248:446058 (1995)). RNAIII, an RNA regulatory molecule encoded by the agr locus, upregulates genes encoding for toxic exomolecules while down regulating genes encoding for surface molecules, resulting in vivo in dissemination and disease (Novick et al. EMBO J. 12:3967–75 (1993); Balaban et al. Proc. Natl. Acad. Sci. USA 92:1619–23 (1995); Moerfeldt et al. EMBO J. 14:4569–77 (1995)). The RNAII locus regulates the expression of RNAIII. The RNAII locus comprises four open reading frames (ORFs), agrA, agrB, agrC, and agrD. The agrA and agrC genes encode for a classical two-component signal transduction pathway, with agrC encoding a signal receptor and agrA the response regulator.
The autoinducers of RNAIII that have been described to date include the agr-independent RNAIII activating protein (RAP) (Balaban et al (1995) supra), and the agrD-derived octapeptide pheromone (Ji et al. Proc. Natl. Acad. Sci. 92:12055–9 (1995)). The agrD-derived octapeptide has also been shown to be part of a “bacterial interference” system that provides a mechanism for different S. aureus strains to compete with each other at an infection site (Ji et al. Science 276:2027–30 (1997)). In this bacterial interference system, the octapeptide activates RNAIII transcription of the strain by which it is produced, while also acting as an inhibitor of RNAIII transcription of other strains of Staphyloccocus. 
In addition to agr, the sar locus also plays a role in regulation of S. aureus virulence factor production. The sar locus comprises a sarA ORF preceded by a triple promoter region interspersed with two putative smaller ORFs (ORF3 and ORF4). The triple promoter system yields three overlapping sar transcripts (sarA, sarC and sarB) (Bayer et al. J. Bacteriol. 178:4563–70 (1996)).
In vivo S. aureus first produce proteins that facilitate bacterial binding to host cells as well as the secreted autoinducer molecules. As the bacterial colony increases in density, the autoinducer molecules accumulate. Upon reaching a threshold concentration, the autoinducers activate RNAIII transcription, which in turn results in virulence factor production. The virulence factors damage and eventually destroy surrounding host cells, which serve as nutritive sources for the S. aureus bacteria and promoting further growth of the colony. Thus, inhibition of RNAIII by suppression of the autoinducers or their receptors is of particular interest in treatment or prevention of S. aureus-mediated disease. Several mechanisms for RNAIII inhibition have been identified, including inhibition of RNAIII by anti-RAP antibodies and by a peptide termed the RNAIII inhibiting peptide (RIP), which competes with RAP (Balaban et al. (1995) supra).
S. aureus causes diseases ranging from minor skin infections to life-threatening deep infections such as pneumonia, endocarditis, meningitis, post-operative wound infections, septicemia, and toxic shock syndrome (Silverstein et al., in Microbiology, Davis et al., eds. (Lippincott, Philadelphia, 1990), pp. 485–506). Hospitalized patients are at particular risk, with over 500,000 nosocomial infections per year (Panlilio, et al., Inf. Contr.and Hasp. Epidem. 13, 582 (1992)). The emergence of drug resistance has made many of the available antimicrobial agents ineffective. Therefore, alternative methods for the prevention and treatment of bacterial infections in general and S. aureus infections in particular are eagerly sought. The instant invention addresses this need and others.